Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients

• ClinicalTrials.gov Identifier: NCT02767193
• Recruitment Status: Completed
• First Posted: May 10, 2016
• Last Update Posted: July 26, 2019
• Sponsor: Judit Pich Martínez
• Information provided by (Responsible Party): Judit Pich Martínez, Fundacion Clinic per a la Recerca Biomédica

Study Description

Brief Summary:

single-center, national clinical trial, phase I, randomized (1: 1: 1: 1), prospective, placebo-controlled, partially masked, parallel group. Patients will be assigned to one of the following four arms: 3 immunizations of dendritic cells / 3 immunizations of dendritic cells with pegylated interferon + / 3 immunizations of placebo / 3 immunizations of placebo with pegylated interferon.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Biological: DCV3; Biological: DCV3 with PEG-INF; Biological: Placebo; Biological: Placebo with PEG-INF	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated HIV in HIV-1 Infected Patients. Prospective, Randomized, Partially Blinded Study
• Study Start Date: May 2016
• Actual Primary Completion Date: May 22, 2019
• Actual Study Completion Date: May 22, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: DCV3; Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus	Biological: DCV3; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus. Patients will receive three immunizations of dendritic cells during weeks 0, 2 and 4
Experimental: DCV3 with PEG-INF; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG-INF	Biological: DCV3 with PEG-INF; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG_INF Patients will receive three immunizations of dendritic cells during weeks 0, 2 and 4 and INF during weeks 4,5 and 6
Placebo Comparator: CD placebo; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded	Biological: Placebo; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded Patients will receive three immunizations saline + 1% albumin during weeks 0, 2 and 4
Placebo Comparator: CD placebo + PEG-INF; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF	Biological: Placebo with PEG-INF; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG_INF Patients will receive three immunizations saline + 1% albumin during weeks 0, 2 and 4 and INF during weeks 4,5 and 6.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with adverse events of grade 3 or higher [ Time Frame: 28 weeks ]
   • Local adverse events of grade 3 or higher (pain and skin reactions including induration)
   • Systemic adverse events of grade 3 or higher (fever, chills, headache, nausea, vomiting, malaise and myalgia)
   • Clinical or laboratory confirmed grade 3 or higher on physical examination or retests adverse events Any event attributable to the vaccine involving a discontinuation of vaccination regime.
2. Virological [ Time Frame: 12 weeks ]
   Proportion of patients with undetectable viral load (<37 copies / mL) at 12 weeks

Secondary Outcome Measures :

1. Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6) [ Time Frame: 6 weeks ]
2. Changes in the specific immune response [ Time Frame: 28 weeks ]
   Measured by ELISPOT visits in weeks 2, 4, 8, 12, 16 and 28 compared to baseline and screening for dendritic cell vaccine and pegylated interferon.
3. Changes in levels of viral reservoir. [ Time Frame: 28 weeks ]
   Measure the proviral DNA visits in the weeks -44, -36, 4, 8, 12, 16 and 28 compared to baseline and screening.
4. Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation [ Time Frame: 28 weeks ]
   In visits at weeks 4, 16 and 28 compared compared to baseline and screening
5. Proportion of patients with viral rebound [ Time Frame: 15 days ]
   Two consecutive obtaining measurements of plasma viral load> 37 copies / mL separated by at least 15 days after discontinuation of antiretroviral therapy.
6. Proportion of patients with autoimmunity markers induced by the vaccine as measured by: antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factors. [ Time Frame: 16 weeks ]
   Evaluation on autoimmunity with antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factor at screening, baseline and week 16.
7. Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12) [ Time Frame: 28 weeks ]
   Weeks 4, 16 and 28 compared to baseline
8. Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline [ Time Frame: week 0 ]
   Proportion of patients with IFN-gamma production in vitro measured by ELISPOT at screening and baseline
9. Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline [ Time Frame: week 0 ]
   Proportion of patients with dendritic cell maturation markers in vitro measured by flow cytometry at screening and baseline
10. Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline [ Time Frame: week 0 ]
    Proportion of patients with T-cell proliferation in vitro measured by CFSE (carboxyfluorescein succinimidyl ester) at screening and baseline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient > 18 years of age;
2. Voluntarily sign informed consent;
3. Men or women with a negative pregnancy test before inclusion in the study;
4. HIV infection tested (with positive antibodies to HIV-1 and a detectable viral load);
5. Patient must be on stable treatment with cART at least 1 year
6. The average of all measurements of CD4 during the year before starting cART should be equal or greater than 350 cells / mm3
7. The number of CD4 + at enrollment must be equal or greater than 450 cells / mm3;
8. Plasma HIV viral load undetectable at least 6 months before the inclusion in the study, at least two determinations (occasional blips above the undetectable level are allowed).

Exclusion Criteria:

1. Treatment with suboptimal regimen (less than 3 antiretroviral drugs) before starting cART;
2. History of C CDC events;
3. Interruption of cART during the inclusion in the study;
4. Pregnancy woman or becoming pregnant in the next months;
5. Active opportunistic infections, or any active infection or cancer within 30 days prior to the screening visit;
6. Therapy with immunomodulatory agents, including cytokines (eg IL-2) and gamma globulins or chemotherapy within 90 days prior to the screening visit;
7. Use of anticoagulant medication;
8. Use of any investigational drug within 90 days prior to study entry;
9. Virological failure prior to antiretroviral treatment and / or mutations that confer resistance to antiretroviral drugs;
10. Uncontrolled psychiatric disorder;
11. Platelet count <80,000 / mm3;
12. Values ??of hemoglobin <12g / dL;
13. Patients with active uncontrolled autoimmune diseases;
14. Using contraindicated drugs in accordance with the Summary of Product Specifications of pegylated interferon;
15. Childbearing, or potential childbearing not using highly effective contraception;
16. Any other problem that according to the investigator could interfere with the evaluation of the objectives.
17. Any contraindication for the use of interferon peg in accordance with the Summary of Product Characteristics.

Contacts and Locations

Locations

Spain

Hospital Clínic

Barcelona, España, Spain, 08036

Sponsors and Collaborators

Judit Pich Martínez

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leal L, Couto E, Sanchez-Palomino S, Climent N, Fernandez I, Miralles L, Romero Y, Gonzalez T, Maleno MJ, Pano B, Pich J, Nicolau C, Gatell JM, Plana M, Garcia F; DCV3-RISVAC04 Study Group. Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon alpha-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial. Front Immunol. 2021 Nov 11;12:767370. doi: 10.3389/fimmu.2021.767370. eCollection 2021.

• Responsible Party: Judit Pich Martínez, Clinical Research Manager, Fundacion Clinic per a la Recerca Biomédica
• ClinicalTrials.gov Identifier: NCT02767193
• Other Study ID Numbers: DCV3/RisVac04; 2015-001795-22 ( EudraCT Number )
• First Posted: May 10, 2016
• Last Update Posted: July 26, 2019
• Last Verified: July 2019

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases